The Effect of Selected Coffee Constituents on Mitochon-Drial Dysfunction In An Early Alzheimer Disease Cell Model

Abstract

Alzheimer disease (AD) is an emerging medical problem worldwide without any cure yet. By 2050, more than 152 million people will be affected. AD is characterized by mitochondrial dys-function (MD) and increased amyloid beta (Aβ) levels. Coffee is one of the most commonly consumed beverages. It has many bioactive and neuroprotective ingredients of which caffeine (Cof), kahweohl (KW) and cafestol (CF) shows a variety of pharmacological properties such as anti-inflammatory and neuroprotective effects. Effects of Cof, KW, and CF were tested in a cel-lular model of AD on MD and Aβ. SH-SY5Y-APP695 cells were incubated with 50μM Cof, 1μM CF and 1μM KW for 24h. The energetic metabolite ATP was determined using a luciferase-catalyzed bioluminescence assay. The activity of mitochondrial respiration chain complexes was assessed by high-resolution respirometry using a Clarke electrode. Expression levels genes were deter-mined using quantitative real-time polymerase chain reaction (qRT-PCR). The levels of amyloid β-protein (Aβ1-40) were measured using homogeneous time-resolved fluorescence (HTRF). ROS levels, cAMP levels, and peroxidase activity were determined using a fluorescence assay. The combination of Cof, KW and CF significantly increased ATP levels. The combination had neither a significant effect on MMP, on activity of respiration chain complexes, nor on A β1-40 levels. cAMP levels were slightly increased after incubation with the combination, but not the peroxi-dase activity. Pyruvate levels and the lactate-pyruvate-ration but not lactate levels were signifi-cantly enhanced. No effect was seen on the expression level of lactate dehydrogenase and py-ruvate dehydrogenase kinase. In some experiments we have tested the single substances. They showed significant results especially in ATP, lactate and pyruvate values compared to the con-trol. The combinations have a lesser effect on mitochondrial dysfunction in cells and none on Aβ production. Whereas ATP levels and pyruvate levels were significantly increased. This suggests a change in glycolysis in neuronal cells harbouring human genes relevant for AD.

Combination of Secondary Plant Metabolites and Micronutrients Improves Mitochondrial Function in a Cell Model of Early Alzheimer’s Disease

“…Deficits are also evident in AD, in which Mg and Fol levels are found to be reduced in brain tissues of patients [ 49 , 50 , 51 , 52 ]. In our studies using SH-SY5Y-APP 695 cells as an AD model, no increase in ATP levels was observed from the single administration of MgOr and Fol [ 26 ] The combination of the three coffee ingredients (Cof, KW, and CF) increased ATP levels [ 25 ], but Cof as single compound had no effect on ATP levels as shown in our experiments. However, it has been described in the literature that Cof affects ATP levels in HepG2 cells and smooth muscle cells [ 53 , 54 ].…”

“…Furthermore, it increases the activities of CAT, SOD, GRX and GPX, and cytoprotective effects of hesperetin against Aβ-induced impairment of glucose transport have been reported [ 24 ]. We recently have shown that HstP reduces ROS levels in SH-SY5Y-APP 695 cells without affecting mitochondrial function or Aβ 1–40 level [ 25 ]. In another study, we showed that magnesium-orotate (MgOr) and folic acid (Fol) reduced Aβ, soluble alpha APP (sAPPα) and lactate levels in SH-SY5Y-APP 695 cells [ 26 ].…”

“…Deficiency leads to impaired methylation of enzymes and promoter regions of genes involved in AD. [ 25 , 26 ]. MgOr is the magnesium salt of orotic acid, showing enhanced bioavailability.…”

Combination of secondary plant metabolites and micronutrients against Alzheimer disease in a SH-SY5Y-APP695 cell model

“…All substances improve the symptoms triggered by AD in different areas of AD. HstP improves mitochondrial dysfunction [42], MgOr and Fol reduce Aβ levels within cells [43] and caffeine, kahwol and cafestol (KCC) affects glycolysis [44]. In this study, we asked ourselves whether a combination of all substances leads to an improvement in all three areas of AD.…”